biostudies-literatureLiang SFunding of Taizhou People’s Hospital (Taizhou, Jiangsu, China2241118https://www.ebi.ac.uk/biostudies/studies/S-EPMC10399481biostudies-literatureUnknown38(1)Prostate cancer (PCa) is a clinically heterogeneous disease with a progressively increasing incidence. Concurrent inhibition of coactivator-associated arginine methyltransferase 1 (CARM1) and histone deacetylase 2 (HDAC2) could potentially be a novel strategy against PCa. Herein, we identified seven compounds simultaneously targeting CARM1 and HDAC2 through structure-based virtual screening. These compounds possessed potent inhibitory activities at the nanomolar level <i>in vitro</i>. Among them, CH-1 was the most active inhibitor which exhibited excellent and balanced inhibitory effects against both CARM1 (IC₅₀ = 3.71 ± 0.11 nM) and HDAC2 (IC₅₀ = 4.07 ± 0.25 nM). MD simulations presented that CH-1 could stably bind the active pockets of CARM1 and HDAC2. Notably, CH-1Journal of enzyme inhibition and medicinal chemistryDiscovery and biological evaluation of novel CARM1/HDAC2 dual-targeting inhibitors with anti-prostate cancer agents.PMC10399481ZL202005QDJJ202101Liang SNiu MMLi JYang LZhang YHe WGeng YXu ZfalseDiscovery and biological evaluation of novel CARM1/HDAC2 dual-targeting inhibitors with anti-prostate cancer agents.Prostate cancer (PCa) is a clinically heterogeneous disease with a progressively increasing incidence. Concurrent inhibition of coactivator-associated arginine methyltransferase 1 (CARM1) and histone deacetylase 2 (HDAC2) could potentially be a novel strategy against PCa. Herein, we identified seven compounds simultaneously targeting CARM1 and HDAC2 through structure-based virtual screening. These compounds possessed potent inhibitory activities at the nanomolar level <i>in vitro</i>. Among them, CH-1 was the most active inhibitor which exhibited excellent and balanced inhibitory effects against both CARM1 (IC₅₀ = 3.71 ± 0.11 nM) and HDAC2 (IC₅₀ = 4.07 ± 0.25 nM). MD simulations presented that CH-1 could stably bind the active pockets of CARM1 and HDAC2. Notably, CH-12023-01-01T00:00:00Z2023 Dec2025-04-27T00:20:29.609Z2025-04-06T17:49:28.821ZS-EPMC103994813752865710.1080/14756366.2023.2241118